Chemotherapy is the standard of care for the treatment of many types of cancer, and alternatives methods for treating cancer are need in situations where chemotherapy is not effective. The human immune system is sometimes able to prevent or slow the growth of cancerous cells through recognition by T cells. In order to improve the ability of immune cells to kill cancerous cells, T cells can be isolated from the blood of a patient and genetically altered to specifically bind proteins expressed on the surface of cancerous cells. When put back into the patient, the modified cells more efficiently target the cancerous cells. CD19 is a protein expressed on cancerous B cells. Brentjens et al. report that T cells altered to bind CD19 can induce remissions of cancer in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med, 2013, 5(177):177ra38.
Chemotherapy agents typically act by killing cancerous cells but they also affect other circulating cells such as T cells. Dasgupta et al. report engineering immune cells to be resistant to cancer drugs in order to prevent T cell death and enhance tumor cell killing during chemotherapy. Biochem Biophys Res Commun, 2010, 391(1):170-5.
Humans generate T- and B-cell antigen receptors primarily by the assembly of Ig V-(D)-J gene segments and somatic hypermutation. Lampreys and hagfish have an alternative system that is based on variable lymphocyte receptors (VLRs), the diversity of which is generated from leucine-rich repeat (LRR) cassettes. Yu et al., report purification and identification of cell surface antigens using lamprey monoclonal antibodies. Immunol Methods, 2012, 386(0): 43-49. See also Yu et al., A lamprey monoclonal VLR antibody recognizes a novel plasma cell antigen, The J of Immunol, 2013, 190, Abstract 114.11; Han et al. Antigen recognition by variable lymphocyte receptors, Science, 2008 321:1834-183; Hirano et al., The evolution of adaptive immunity in vertebrates, Adv Immunol, 2011, 109:125-57; WO 2013/078425; US 2011/0230374; WO 2010/065407; and WO 2008/016854.
References cited herein are not an admission of prior art.